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Biomedical subjects

K Hirakawa

Publications and source records attributed to K Hirakawa.

At least 19 recordsLinked to original sources
PubMed1999

GT1b in human metastatic brain tumors: GT1b as a brain metastasis-associated ganglioside.

We studied ganglioside expression in 12 human metastatic brain tumors metastasized from colon (4), renal (3), lung (2), esophagus (1), pancreas (1), and mammary (1) carcinomas. GM3 was the major common ganglioside expressed in brain metastatic tumor tissues, and GT1b was also present in all the metastatic brain tumor tissues. The latter was identified by TLC-immunostaining and characterized structurally by secondary ion mass spectrometry combined with 'Far-Eastern blot'. The immunohistochemical analysis of frozen tissue sections confirmed localization of GT1b in the tumor cell membrane or cytosol. GT1b was shown to be expressed both in the primary colon carcinoma and the metastasis of a single patient by immunohistochemical procedure. In systemic carcinomas without brain metastasis, GM3 was a common major component, but no GT1b was detected. These findings indicate that GT1b is a brain metastasis-associated ganglioside. We speculate that the presence of GT1b would be a useful marker for estimating metastatic potentials to the brain.

Adenocarcinoma↗
PubMed1998

Primary sclerosing pancreatitis and cholangitis.

CONCLUSION: The clinical course of our patient suggests the association between chronic pancreatitis and primary sclerosing cholangitis (PSC), as well as the usefulness of prednisolone for the treatment of this condition. BACKGROUND: Although alterations in the pancreatic duct have been reported, the association between chronic pancreatitis and PSC remains uncertain. METHODS AND RESULTS: A long-term follow-up case of chronic pancreatitis accompanied by PSC is presented. A 58-yr-old man complaining of epigastric distress was admitted to our hospital in July 1990. Endoscopic retrograde cholangio-pancreatography (ERCP) showed a stricture of the distal common bile duct and a narrowing of the main pancreatic duct (MPD) with mild ectasia of its branches in the head of the pancreas. ERCP taken in June 1992 revealed localized narrowings in both the right and the left main hepatic ducts, and irregularity of the MPD through the entire pancreas. An ERCP taken in June 1996 showed a progression of the narrowings of the bile ducts. The patient was diagnosed as having chronic pancreatitis accompanied by PSC. ERCP revealed a remarkable improvement of the bile ducts after 4 wk of treatment with prednisolone.

Anti-Inflammatory Agents↗
PubMed1998

Immunolocalization of matrix metalloproteinases in rabbit carotid arteries after balloon denudation.

Extracellular matrix-degrading enzymes may play a key role in vascular remodeling after arterial wall injury. We investigated the immunolocalization of matrix metalloproteinases (MMPs) in rabbit carotid arteries after balloon denudation. Positive immunostaining for MMP-1, -2, -3, and -9 appeared through the neointima 1 week after balloon denudation. The localization of immunopositive smooth muscle cells (SMCs) for MMP- 1, -3, and -9, particularly for MMP-9, was almost similar to that of replicative SMCs and became confined to the luminal surface layer of the neointima at later time periods. However, MMP-2-positive SMCs appeared also in the basal layer of the neointima at 2 weeks, increased at 4 weeks, and then totally occupied the neointima at 6 weeks. The MMP-2-positive SMCs in the basal layer of the neointima at 4 and 6 weeks were negative for proliferation-associated antigens and were surrounded by extracellular matrix proteins. Our results suggest that all MMPs act in coordination to promote replication and migration of SMCs in the earlier phases of neointimal formation and that MMP-2 independently contributes to the later stages by facilitating the migration but not replication of SMCs from the media to the intima.

Animals↗
PubMed1998

Recurrence in meningeal hemangiopericytomas.

BACKGROUND: Meningeal hemangiopericytomas are more aggressive than typical meningiomas, with a high rate of recurrence and distant metastases. The question of whether a correlation exists between prognosis and histologic features remains controversial. CASE DESCRIPTION: We report two cases of recurrent meningeal hemangiopericytomas. Although local growth control of the tumor was obtained by tumor removal and irradiation in a 38-year-old male patient (Case 1) with a recurrent tentorial tumor, the tumor disseminated and metastasized extracranially within a short period after treatment, leading to rapid deterioration. Another 38-year-old female patient (Case 2) with a recurrent orbital tumor had a favorable outcome after tumor removal. The Ki-67 proliferative index using the MIB-1 monoclonal antibody increased as the tumor recurred in Case 1 (2.5%, 7.9%, and 15.7%), but did not change between primary and recurrent tumors of Case 2 (4.2%, 3.1%). Immunostaining for p53 protein in Case 1 was negative at the first resection, and became positive at the second and third resections, whereas in Case 2, it was negative in both the primary and recurrent tumors. CONCLUSIONS: Our results suggest that p53 protein accumulation with a high proliferative potential is a useful marker to estimate malignant progression in meningeal hemangiopericytomas.

Adult↗
PubMed1998

Results of 2-stage reimplantation for infected total knee arthroplasty.

Optimum treatment of the infected total knee arthroplasty has not been clearly established. To clarify the efficacy of two-stage reimplantation, experience with 66 infected total knee arthroplasties in 64 patients who had been treated with 2-stage reimplantation total knee arthroplasty between September 1980 and October 1993 was reviewed. Of these, 55 knees in 54 patients were available for follow-up examinations at an average of 61.9 months (range, 28-146 months). The initial diagnoses were rheumatoid arthritis (14 knees) and osteoarthritis (41 knees). Reimplantation was successful in 80.0% of knees with low-virulence organisms (coagulase-negative Staphylococcus, Streptococcus), 71.4% with polymicrobial organisms, and 66.7% with high-virulence organisms (methicillin-resistant Staphylococcus aureus). Reimplantation was successful in 82% of patients with osteoarthritis and in 54% of patients with rheumatoid arthritis (P = .024). The success rate was 92% if infection occurred after primary arthroplasty but only 41% if after multiple previous knee operations (arthroscopy, osteotomy, or revision total knee arthroplasty) (P < .001).

Adult↗
PubMed1998

Establishment of lymph node metastatic model for human gastric cancer in nude mice and analysis of factors associated with metastasis.

The actual mechanisms responsible for lymph node metastasis in gastric cancer are still unclear. To investigate the mechanisms of lymph node metastasis in gastric cancer, we established a lymph node metastatic model for human scirrhous gastric carcinoma. Lymph node metastasis had frequently developed after orthotopic implantation of OCUM-2M LN derived from a scirrhous gastric cancer cell line, OCUM-2M, which had low capacity for lymph node metastasis. We elucidated the different characteristics including binding ability, migratory capacity and immunoresponses induced by the cell surface molecules of these two cell lines. The binding ability to Matrigel and migratory capacity of OCUM-2M LN cells were significantly greater than those of OCUM-2M cells. On flow cytometric analysis, both OCUM-2M and OCUM-2M LN cells strongly expressed HLA-I (99.5 and 97.1%) and LFA-3 (76.6 and 99.2%) in level of expression between the two cell lines, but neither cell line expressed HLA-II (0.0 and 0.0%), B7-1 (0.0 and 0.0%) or B7-2 (0.4 and 0.3%). ICAM-1 expression in OCUM-2M LN cells was weaker (0.7%) than that in OCUM-2M cells (36.8%). Strong adhesiveness and cytotoxicity of mononuclear lymphocytes for OCUM-2M cells were observed in adhesion and cytotoxic assays, both of which were significantly decreased by the addition of anti-ICAM-1 antibodies. On the other hand, the adhesiveness and cytotoxicity of OCUM-2M LN cells were significantly less than those of OCUM-2M cells, and were not affected by the addition of anti-ICAM-1 antibodies. These findings suggest that decreased ICAM-1 expression in a new gastric cancer cell line with a high rate of lymph node metastasis may in turn decrease immune responses mediated through LFA-1-dependent effector cell adhesion, and that this escape from the immunosurveillance system may be one of the factors inducing lymph node metastasis. In conclusion, we established a gastric cancer cell line, OCUM-2M LN, with a high rate of lymph node metastasis. An in vivo lymph node-metastatic model with this cell line should be useful for analysing the mechanism and therapeutic approach of lymph node metastasis.

Adenocarcinoma, Scirrhous↗
PubMed1998

Adhesion polypeptides are useful for the prevention of peritoneal dissemination of gastric cancer.

We examined the effect of adhesion polypeptides on the adhesion and invasiveness of gastric cancer cell lines. We previously reported the establishment of an extensively peritoneal-seeding cell line, OCUM-2MD3, from a poorly seeding human scirrhous gastric carcinoma cell line, OCUM-2M. Both alpha2beta1 and alpha3beta1 integrin expression was markedly increased on OCUM-2MD3 cells compared with OCUM-2M cells, and the ability of OCUM-2MD3 cells to bind to the extracellular matrix (ECM) was also significantly higher than that of OCUM-2M cells. The adhesion polypeptides, YIGSR and RGD, and two RGD derivatives significantly inhibited the adhesion of OCUM-2MD3 cells to the submesothelial ECM, while not inhibiting the adhesiveness of OCUM-2M cells and two well differentiated human gastric cell lines, MKN-28 and MKN-74. The YIGSR and RGD peptides also significantly inhibited the invasiveness of OCUM-2MD3 cells. The survival of nude mice with peritoneal dissemination given YIGSR sequence intraperitoneally was obviously longer than that of untreated mice. The survival of mice treated with RGD was also improved, and this effect was increased using the RGD derivatives, poly(CEMA-RGDS) and CM-chitin RGDS. These polypeptides appear to block the binding of integrins, which are expressed on OCUM-2MD3 cells, to the submesothelial ECM, and consequently inhibit peritoneal implantation. The peritoneal injection of adhesion polypeptides may be a new therapy against the dissemination of scirrhous gastric cancer, and may be useful for the prevention of dissemination in high-risk patients.

Adenocarcinoma, Scirrhous↗
PubMed1998

An assessment of local curability of endoscopic surgery in early gastric cancer without satisfaction of current therapeutic indications.

BACKGROUND AND STUDY AIMS: Therapeutic endoscopy for early gastric cancer has been established with strict criteria for indications. In the present study, we evaluated the efficacy of endoscopic treatment in cases that did not fulfil the standard therapeutic criteria, consisting of well differentiating mucosal adenocarcinomas less than 2 cm in size and without an ulcer or a scar. PATIENTS AND METHODS: Sixty nine early gastric cancers in 64 patients that did not fulfil the standard criteria were treated endoscopically, and a rate of cure was retrospectively assessed during a mean follow-up of 5.2 years. Endoscopic treatment consisted of mucosal resection or thermal methods, or both. RESULTS: Curative resection was achieved in 19/20 (95%) of cases which came into one of the following categories, all being well differentiated adenocarcinomas, less than 3.0 cm in size, without ulcer or the scar of an ulcer, with invasion limited to mucosal layer (depth m); tumors less than 2.0 cm, with an ulcer or scar, depth m; tumors less than 2.0 cm, without ulcer or scar, invading the submucosa but in which invasion was limited to the superficial portion (depth sm-1); and poorly differentiated tumors less than 1.0 cm in size, without an ulcer or scar, depth m. The rate of cure in this group was statistically similar to the cure rate of cases that fulfilled the standard criteria (98%). CONCLUSIONS: Our retrospective results suggest that the indications for curative treatment of early gastric cancer could be expanded. Prospective studies are required.

Adenocarcinoma↗
PubMed1998

Posthyperventilatory steal response in chronic cerebral hemodynamic stress: a positron emission tomography study.

BACKGROUND AND PURPOSE: The alteration of regional cerebral blood flow (CBF) during and after hyperventilation was measured using positron emission tomography (PET) to determine the circulatory response induced by daily respiratory changes in the cerebral area under chronic hemodynamic stress. METHODS: Three normal volunteers and 12 patients with an obstruction of major cerebral arteries underwent PET measurements of the CBF after an injection of H2(15)O: (1) in the resting condition, (2) during hyperventilation (HV scan), (3) 1 to 3 minutes after hyperventilation (post-HV scan), (4) during the inhalation of 5% CO2, and (5) after an injection of acetazolamide. Eleven patients also underwent a 15O gas study to measure CBF, oxygen extraction fraction (OEF), and cerebral blood volume (CBV). RESULTS: (1) In 9 patients, the CBF value in the post-HV scan was lower than that in the HV scan in 1 or more regions in the area of the obstructed arteries, although the PaCO2 level during the post-HV scan was higher than that during the HV scan in all patients. All control regions in the patients and in the normal volunteers showed an elevated CBF in the post-HV scan compared with the HV scan. (2) The negative post-HV response (posthyperventilatory steal) was prominent in 4 patients with moyamoya vessels and in another 5 patients with atherosclerotic disease who had PET evidence of hemodynamic stress (elevated CBV or OEF). (3) The regional pre- to post-HV change in CBF was significantly correlated with the CBF responses to acetazolamide and CO2. CONCLUSIONS: Vasodilatation after the termination of hyperventilation in the normal areas induces a steal response in the cerebral area suffering from hemodynamic stress and may cause profound hypoperfusion in everyday situations. This phenomenon may be important to our understanding of the clinical symptoms and the natural course of chronic cerebral occlusive disease bearing hemodynamic stress.

Acetazolamide↗
PubMed1998

Nitric oxide production and energy state in the heart after endotoxin administration.

To evaluate nitric oxide (NO) production and the energy state of the heart after endotoxin administration, Wistar rats were injected i.p. with 10 mg/kg Escherichia coli lipopolysaccharide (endotoxin). Morphologic changes, plasma nitrite concentration, expression of inducible NO synthase (iNOS), and cardiac energy state, as reflected by several metabolites, were observed chronologically 0 (control), 4, 6 and 8 h after endotoxin administration. Electrocardiography (ECG) demonstrated arrhythmia after endotoxin administration. Biochemically, NO production increased in blood and iNOS increased in the heart. The amount of myocardial beta-ATP measured by 31P magnetic resonance spectroscopy (31P-MRS) increased transiently and then decreased. This transient increase might be a hyperdynamic response to endotoxin administration. At 4 and 6 h after endotoxin administration, pH measured by 31P-MRS was slightly decreased, but this decline was not statistically significant. On the other hand, the amount of lactate in heart samples increased in the 1H magnetic resonance spectra (1H-MRS). Ultrastructurally, in cardiovascular tissue, intracytoplasmic organelles were observed to be injured in blood vessels and cardiomyocytes associated with mast cell infiltration. These results suggest significant metabolic and morphologic abnormalities in the heart after endotoxin administration.

Animals↗
PubMed1998

Expression of intercellular adhesion molecule-1 in invasive breast cancer reflects low growth potential, negative lymph node involvement, and good prognosis.

To understand the role of intercellular adhesion molecule-1 (ICAM-1) in tumor progression in the host, we examined ICAM-1 expression in breast cancer by immunohistochemistry. This study included 274 female patients with invasive breast cancer, with a median follow-up of 98 months. The molecule was identified in formalin-fixed, paraffin-embedded primary tumors, and the relationship to clinicopathological factors and prognosis was analyzed. ICAM-1 expression occurred in 50.3% of patients. ICAM-1 expression had negative correlation to tumor size (P = 0.003), lymph node metastasis (P < 0.0001), tumor infiltration (P = 0.003), nuclear pleomorphism (P = 0.004), and nuclear grade (P = 0.042). Patients with ICAM-1-positive tumors had better relapse-free and overall survival than those with negative tumors (P < 0.0001 and P = 0.0003, respectively). These results suggest that expression of ICAM-1 on cancer cells might have a role as a suppressor of tumor progression under the host immune surveillance system.

Breast Neoplasms↗
PubMed1998

[p53 and Bax protein expression as predictor of chemotherapeutic effect in gastric carcinoma].

This study was performed to estimate p53 and Bax overexpression as a predictor of the response to chemotherapy of patients with gastric cancer. The subjects were 20 patients with stage IV gastric cancer and 3 with locally recurrent lesions treated with 5-fluorouracil (5-FU) and low-dose cisplatin (CDDP) for 4 weeks. Of the total 23 patients, there were 10 responders: 2 showing complete response (CR) and 8, partial response (PR). Carcinoma biopsy specimens of all were obtained endoscopically with anti-p53 and anti-Bax antibodies. Of the 10 responders, 7 were in the negative p53 staining group, while of the 13 non-responders, 11 were in the positive p53 staining group (p = 0.013). But no correlation was demonstrated between the chemotherapeutic effect and Bax staining alone. Moreover, among the p-53-positive cases, the patients with Bax-negative tumors were all chemoresistant. Therefore, immunohistochemical identification of p-53 and Bax prior to chemotherapy may be a useful predictor for choice of non-responders to chemotherapy.

Adenocarcinoma↗
PubMed1998

[Correlation between pyrimidine nucleoside phosphorylase (PyNPase)/platelet-derived endothelial cell growth factor and histological prognostic factor, and influences of 5'-deoxy-5-fluorouridine (5'-DFUR) administration on PyNPase levels. 5'-DFUR Joint Research Group in the Osaka Area for Gastric Cancer].

PURPOSE: Pyrimidine nucleoside phosphorylase (PyNPase), among which thymidine phosphorylase (dThdPase) exists mainly in human tumor tissues, is an enzyme to convert 5'-deoxy-5-fluorouridine (5'-DFUR) to 5-fluorouracil. Recently, it was reported that dThdPase was identical to platelet-derived endothelial cell growth factor, angiogenetic factor. Therefore, we expect that there is possibility of dThdPase being a prognostic factor. METHODS: We investigated for a possible correlation between PyNPase activities in tumor tissues and prognostic factors of histological findings, examined the influences of preoperative oral 5'-DFUR administration to PyNPase levels and investigated for a correlation between HPLC methods and ELISA methods in patients with gastric cancer. RESULTS: Higher levels of PyNPase were observed in patients with advanced t,n,v, and ly factors. PyNPase levels decreased by 5'-DFUR in patients with differentiated cases. A high correlation was found between HPLC and ELISA methods. CONCLUSION: This study suggests that we must investigate possibility of PyNPase being a prognostic factor in more detail.

Antineoplastic Agents↗
PubMed1997

Effect of femoral head diameter on tissue concentration of wear debris.

Although several studies have reported the physical properties of debris particles in tissues adjacent to failed total joint implants, few have correlated the results of particle analysis with other clinical and implant variables believed to influence implant wear. We retrospectively analyzed 41 fibrous membranes (from 35 patients) adjacent to failed acetabular cups from a single manufacturer and studied the relationship between three different femoral head sizes (26, 28, and 32 mm) and the characteristics of wear debris in the adjacent tissues. All total hip prostheses consisted of modular cobalt-chromium alloy femoral heads articulating with titanium-alloy-backed ultrahigh molecular weight polyethylene (UHMWPE) acetabular components from a single manufacturer. Large femoral head diameter (32 mm) was found to correlate significantly with large particle size (diameter and surface area, p < 0.05), high tissue concentration of particles (particle volume/gram of tissue, p < 0.01), and high rate of particle production (particles volume/month, p < 0.05). The results of these quantitative assays support the findings of radiographically based clinical studies that show higher volumetric wear associated with 32 mm femoral head components.

Adult↗
PubMed1997

MELAS presenting as migraine complicated by stroke: case report.

A case of MELAS (mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes) which presented as migraine complicated by stroke is reported. Strokes associated with migraine have often been reported, but the mechanism remains unclear and may include a variety of pathologies. MELAS also presents with migrainous headache, vomiting, and stroke-like symptoms. Magnetic resonance imaging demonstrates characteristic findings. MELAS should be considered in the differential diagnosis of infarct-like lesions with migrainous headaches in young adults, especially if the symptoms fluctuate and are accompanied by a homonymous hemianopia.

Adult↗
PubMed1997

Smooth muscle cell proliferation, elastin formation, and tropoelastin transcripts during the development of intimal thickening in rabbit carotid arteries after endothelial denudation.

Extracellular matrix formation and smooth muscle cell proliferation are two major factors contributing to the development of intimal thickening after arterial injury. We investigated the elastin formation, tropoelastin transcripts, and proliferation of smooth muscle cells during the development of intimal thickening in rabbit carotid arteries after balloon endothelial denudation. Tropoelastin transcripts, identified by in situ hybridization using a digoxigenin-labeled probe, and elastin staining in the thickened intima were minimal 1 week after endothelial denudation when smooth muscle cell proliferation appeared throughout the thickened intima. A strong signal for tropoelastin transcripts was seen in the basal layer of the thickened intima 2 weeks after endothelial denudation, and then in the surface layer of the thickened intima 4 weeks after endothelial denudation. Immunohistochemistry for proliferating cell nuclear antigen and Ki-67, both markers for proliferating cell nuclei, showed that tropoelastin transcripts and elastin formation increased when smooth muscle cells enter quiescence after the end of the proliferative phase in the intima. Our findings strongly suggest that elastin synthesis and smooth muscle cell proliferation are tightly regulated during the repair of arterial wall injury.

Animals↗